Gram-Positive Infections

Chapter 108 Gram-Positive Infections






GRAM-POSITIVE CELL STRUCTURE AND PATHOGENICITY


Morphologically, gram-positive bacteria are composed of a cell wall, a single cytoplasmic membrane, and cytosol. The cell wall is a thick, coarse structure that serves as an exoskeleton.1 Buried within the cell wall are enzymes called transpeptidases, commonly referred to as penicillin-binding proteins (PBPs).1,10 PBPs are a group of enzymes responsible for the building and maintenance of the cell wall.


In addition to a thick cell well, most gram-positive bacteria have other protective mechanisms.10,11 One of these mechanisms is an outer capsule or biofilm that extends beyond the cell wall itself and interfaces with the external milieu.1,11 Hydrolase enzymes located within the cytoplasmic membrane, called β-lactamases, serve a protective role for the bacteria.1,11 Once attacked by the hydrolases, the β-lactam antibiotics are no longer capable of binding to PBPs in normally susceptible bacteria.1,10,12


Peptidoglycan is the basic structural component of the cell wall of gram-positive bacteria, accounting for 50% to 80% of the total cell wall content.10,11 Like endotoxin, peptidoglycan is released by bacteria during infection, reaches the systemic circulation, and exhibits proinflammatory activity.11 Lipoteichoic acids found in the gram-positive cell wall have both structural and epithelial adherence functions.10 Lipoteichoic acid induces a proinflammatory cytokine response, the production of nitric oxide, and may lead to cardiovascular compromise.10


In addition to structural components, gram-positive organisms produce soluble exotoxins that may play a role in the pathogenesis of sepsis. Much attention is focused on the roles of superantigenic exotoxins that promote the massive release of cytokines, potentially leading to shock and multiorgan failure in both human and veterinary patients.10,12,13



STREPTOCOCCAL INFECTIONS


The genus Streptococcus consists of gram-positive cocci arranged in chains. These are fastidious bacteria that require the addition of blood or serum to culture media.10,14,15 They are nonmotile and non–spore forming. Most are facultative anaerobes and may require enriched media to grow. Streptococci are generally commensal organisms found on the skin and mucous membranes, and are ecologically important as part of the normal microflora in pets and humans.14,15 However, several species of streptococci are capable of causing localized or widespread pyogenic infections in companion animals.15


Streptococci may be grouped superficially by how they grow on blood agar plates as either hemolytic or nonhemolytic.10,12 The type of hemolytic reaction displayed on blood agar has been used to classify the bacteria as either α-hemolytic or β-hemolytic. β-Hemolytic species are generally pathogenic, and nonhemolytic or α-hemolytic members of the genera have been viewed traditionally as contaminants or unimportant invaders when isolated.12,15


Streptococci are also classified serologically based on species-specific carbohydrate cell wall antigens, with groups designated A through L.14,15 Group A streptococci (Streptococcus pyogenes) cause pharyngitis, glomerulonephritis, and rheumatic fever in humans.12,14 Although dogs may become colonized transiently with this organism, group A streptococci rarely cause illness in dogs and cats.10,12,14,15 Therapy is not generally indicated, but these organisms are susceptible to most β-lactam agents, macrolides, and chloramphenicol; resistant strains may be treated with cephalosporins.15


Similarly, group B or C streptococci are rare causes of illness in immunocompetent pets.14,15 Infections with group B Streptococcus agalactiae have been associated with neonatal sepsis and fading puppy syndrome.15 Sporadically, cases of endometritis, wound infections, pyelonephritis, lymphadenitis, neonatal sepsis, and pneumonia due to infection with β-hemolytic group C streptococci have been documented in dogs and cats.16,17 Species included in this serologic group include Streptococcus equi subsp zooepidemicus, and Streptococcus dysgalactiae.14,16,17 Although culture and susceptibility testing is always advocated, effective therapies for these infections are generally the same as those described for the group A streptococci.15,17


Group G streptococci are common resident microflora and are the cause of most streptococcal infection in dogs and cats.10,12,15 The most common isolate is Streptococcus canis.10,15 The main source of infection with this pathogen in dogs is the anal mucosa, with young cats more commonly acquiring infection from the vagina of the queen or via the umbilicus.15 Infection spreads rapidly in neonatal kittens and is often fatal during the first week of life in affected cats.15 S. canis may be isolated from adult cats with abscesses, urinary tract infections, arthritis, metritis, or mastitis, and from kittens with lymphadenitis, pneumonia, or neonatal septicemia.10,15


S. canis is generally an opportunistic pathogen of dogs and is isolated from an array of nonspecific infections, including wounds, the mammary gland, urogenital tract, skin, and ear canal.15 S. canis is also responsible for canine prostatitis, mastitis, abscesses, infective endocarditis, pericarditis, pyometra, sepsis, discospondylitis, and meningoencephalomyelitis.11,15,18 S. canis has been implicated in cases of fading puppy syndrome, causing polyarthritis and septicemia in affected pups.15


Despite 50 years of penicillin use in animals, there is no documented mechanism of resistance to the drug in β-hemolytic group G streptococci; penicillin G and ampicillin are therefore effective for most infections.2,11,15 Chloramphenicol, potentiated sulfonamides, and most cephalosporins are also usually efficacious. Susceptibility to veterinary-approved fluoroquinolones is negligible and generally discouraged.19 Streptococcus spp are generally not considered susceptible to aminoglycosides, owing to poor transport across the cytoplasmic membrane.2 However, the synergistic combination of a β-lactam agent with an aminoglycoside remains an appropriate treatment for animals with streptococcal bacteremia or endocarditis.2 In critically ill patients with disseminated infection, long-term (≥6 weeks) therapy is generally indicated. Combination therapy is recommended for cases of infective necrotizing fasciitis (see section on Empiric Antibiotic Strategies later in chapter), endocarditis, or when polymicrobial infections are suspected.


Streptococcal toxic shock syndrome (STTS), with or without necrotizing fasciitis, is recognized as an emerging syndrome in dogs (see Chapter 115, Necrotizing Soft Tissue Infections).10,15 The most common infection in animals with STTS appears to be the lung, with affected dogs suffering from acute or peracute suppurative bronchopneumonia. Some case histories have included failed attempts to treat patients with enrofloxacin and nonsteroidal antiinflammatory agents.15,19 Cases of STTS-associated septicemia are often fatal, whereas most dogs with necrotizing fasciitis alone survive with rapid, appropriate medical therapy and aggressive surgical resection.20


The most likely pathogenesis for STTS and necrotizing fasciitis starts with minor trauma. The dog then licks its wounds and seeds S. canis from the oral mucosa into the wound.20,21 The bacteria proliferate, typically resulting in painful, rapidly developing cellulitis, skin discoloration, and often signs of systemic illness.15,20,21 Prompt recognition and aggressive surgical debridement are imperative.15 Clindamycin has proven to be a valuable treatment in affected animals.15 Chloramphenicol, erythromycin, and β-lactam antibiotics also may be effective.15 Culture and susceptibility testing is important, because similar toxic shock–like diseases in dogs may be caused by bacteria other than streptococci. Gram staining of tissues or fluids should be helpful in ascertaining the morphology of the infecting agent, particularly in acute infections.15 A similar syndrome in young cats with suppurative lymphadenopathy caused by group G streptococci has been reported.10,15



ENTEROCOCCAL INFECTIONS


Enterococcus species are facultative anaerobic cocci that demonstrate intrinsic and acquired resistance to multiple antibiotics.8 Enterococci (previously group D streptococci), as the name implies, are commensal bacteria that inhabit the alimentary tract of animals and humans.4,10,14 Enterococcal infections were previously considered rare, and not especially virulent, in companion animals.14 They typically are recovered from mixed infections in which it is difficult to assess their role; they are assumed to be commensal organisms “along for the ride” with other more virulent organisms such as anaerobes and gram-negative enteric bacteria. Such a priori assumptions can no longer be made, because pathogenic and drug-resistant enterococci are recovered increasingly from hospitalized patients.3,4 Similarly, the presence and expression of virulence genes in some enterococcal species implies that these organisms are an important consideration in the treatment of serious gram-positive infections.3,4,7,14,15


Postoperative wound and urogenital infections are seen most commonly; however, enterococcal cholangiohepatitis, peritonitis, vegetative endocarditis, mastitis, and blood-borne infections have been reported in companion animals.4,15 Many enterococci are intrinsically resistant to numerous antibiotics, and the development of MDR enterococci is thought to result from both inappropriate antibiotic usage and poor infection control measures in hospitalized patients.2-4,8,10 The vast majority of clinical isolates belong to the species Enterococcus faecalis, although E. faecium remains the species that exhibits a disproportionately greater resistance to multiple antibiotics.7,8


E. faecium is largely of interest because of increasing resistance to vancomycin, which until recently was effective for almost all penicillin-resistant enterococci.10 Strains that remain sensitive to vancomycin may be resistant to a wide range of drugs that are commonly selected for empiric treatment of intensive care patients.7,8 Although the veterinary literature is sparse, there are recent and serious concerns of acquired antibiotic resistance by E. faecalis and E. faecium. There is a lack of host specificity among various bacterial strains that suggests that cross-colonization of resistant strains may occur from one species to another.7,8,22 E. faecium often possesses inherent and acquired resistance to many drug classes, including the fluoroquinolones, clindamycin, macrolides, and potentiated sulfonamides.7,8 Unlike most streptococci, the enterococci are often inhibited, but not killed, by penicillins and are generally resistant to cephalosporins.2 Moreover, although enterococci do not intrinsically produce β-lactamases, production of these enzymes by the bacteria may be induced by exposure to β-lactamase inhibitor drugs. As such, it is of no benefit to prescribe amoxicillin-clavulanate or ampicillin-sulbactam if the pathogen is sensitive to the aminopenicillin alone.


Of the 52 E. faecium isolates obtained from clinical patients at the Ryan Veterinary Hospital of the University of Pennsylvania, 71% were resistant to ampicillin (S. Rankin, personal communication). One of the few effective modes of therapy takes advantage of antibiotic synergy; penicillins alone only arrest their growth and aminoglycosides are without effect except at very high concentrations, but the combination of both drugs effectively kills the organism.4 This high-dosage synergy approach is among the most effective pharmacologic means to clear infection and, unless there is compelling evidence that other potentially safer antibiotic regimens are effective both in vivo and in vitro, the combination of gentamicin plus a cell wall–active agent (generally ampicillin) remains a gold standard for critically ill veterinary patients.22


Unfortunately, some enterococci are becoming resistant to aminoglycosides, even when coadministered with ampicillin, leaving the clinician with few alternatives to eradicate the infection.4 In some cases, the only effective drugs are glycopeptides, such as vancomycin, but this drug should be viewed as an absolute last resort.4,8 Vancomycin has a narrow spectrum and is potentially nephrotoxic (see Chapter 200, Miscellaneous Antibiotics).1 Clinical experience with vancomycin is limited in veterinary medicine.

Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Gram-Positive Infections
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